Chronic toxicity evaluation of ethanolic stem bark extract of Randia (Xeromphis) nilotica Stapf. (Rubiaceae) in Wistar rats

Background: Randia nilotica is known in northern Nigeria as Gial-goti, but has also been reported to be widespread in Sudan and India. The plant is used traditionally for its ethno-medicinal claims in managing mental-illnesses, convulsion or epilepsy, jaundice, infertility, snake bites and other ailments. The leaf, root and stem bark of the plant had been scientifically validated for CNS depressant activity and the stembark is particularly used for CNS-related disorders. However, information related to the toxicity potential of the plant is not available. Objective: To investigate the effect of 90-days administration of ethanol stem-bark extract of the plant on some physiological-biomarkers and vital-organs’ histology. Methods: Oral median-lethal dose (LD50) estimated from acute-toxicity test and extract doses of 250, 500, 1000mg/kg for 3-groups of 20-rats each and normal-saline control group were used. The rats were euthanized on the 90th-day following daily oral treatments per-body-weight. Blood-samples in plain and anticoagulated (EDTA) sample-bottles for biochemical and haematological analyses were collected from each group and vital-organs isolated, weighed and kept in fixatives for histo-analyses. Result: The oral acute extract-administration up to 5000mg/kg caused no observable toxic-sign or mortality. PCV, Hb and RBC counts decreased significantly at 500 and 1000mg/kg, but only at 1000mg/kg for MCV, with no significant changes in other haematological-indices. Significant increase in blood-urea-nitrogen at all test-doses and in high-density lipoprotein at 250mg/kg occurred. Brain-weight was significantly decreased and all organs histologically showed blood-vessels congestion and inflammatory-cells’ infiltration, in addition to dose-dependent neuronal-degeneration and cerebral-oedema in brain, lymphocytes’ depletion in spleen, necrositic-hepatocytes, myocardial-haemorrhage with oedematous-fragmentations and glomerular-atrophy, haemorrhage, tubular-necrosis, glomerular hypercellular-vacuolation and Bowman’s-capsule adhesion to parietal surface. Conclusion: Haematological, biochemical and histological analysis revealed evidence of chronic toxicity to various major organ systems. In addition to dose, duration of use also contributes to the toxic effects of the plant. Key-words: Randia-nilotica, stem-bark, ethanol extract, chronic-toxicity, rat